A series of eight variant haplotypes of the glucuronidase gene complex in mice are now available. Included among them are various combinations of five alleles of the structural gene (Gus) and four alleles of a closely linked regulatory locus (Gur) controlling enzyme synthesis in response to hormonal induction. We propose to characterize these variants functionally at the mRNA level and sturcturally in terms of cDNA and genomic DNA sequences. Functional studies will use a new enzymatic assay for glucuronidase mRNA activity and a cDNA clone of the Gus sequence to assay mRNA concentration. This initial clone will also be used as a probe to compare the structure of variant regulatory sequences, both by direct examination of genomic DNA and in the form of recombinant DNA copies of cDNA and genomic DNA. This will also allow us to examine the structure of variant mRNA sequences as recombinant DNA copies. In addition to the eight available haplotyes, we plan to examine new alleles of the structural and regulatory loci, and additional combinations of alleles, as these become available. A project to obtain new alleles is described in an accompanying proposal by V.M. Chapman. Our goals are to gain new insights into details of mammalian gene regulation and to correlate structure with function in one mammalian regulatory sequence.